Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls

Abstract

Purpose

The fusion gene BCR-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BCR-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls.

Methods

Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation.

Results

We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP.

Conclusion

We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.

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Correspondence to R. de Cássia Viu Carrara.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the FMRP-USP Hospital and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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de Cássia Viu Carrara, R., Fontes, A.M., Abraham, K.J. et al. Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls. Clin Transl Oncol 20, 542–549 (2018). https://doi.org/10.1007/s12094-017-1751-x

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Keywords

  • Chronic myeloid leukemia
  • CD34+ cells
  • BCR-ABL
  • Gene expression
  • Chronic phase
  • microRNA